Default polyfunctional T helper 1 response to ample signal 1 alone

CD4^(+)T cells integrate well-defined signals from the T-cell receptor(TCR)(signal 1)and a host of costimulatory molecules(signal 2)to initiate clonal expansion and differentiation into diverse functional T helper(Th)subsets.However,our ability to guide the expansion of context-appropriate Th subsets by deploying these signals in vaccination remains limited.Using cell-based vaccines,we selectively amplified signal 1 by exclusive presentation of an optimized peptide:MHC II(pMHC II)complex in the absence of classic costimulation.Contrary to expectations,amplified signal 1 alone was strongly immunogenic and selectively expanded highaffinity TCR clonotypes,despite delivering intense TCR signals.In contrast to natural infection or standard vaccines,amplified signal 1,presented by a variety of professional and nonprofessional antigen-presenting cells(APCs),induced exclusively polyfunctional Th1 effector and memory cells,which protected against retroviral infection and tumor challenge,and expanded tumor-reactive CD4^(+)T cells otherwise rendered unresponsive in tumor-bearing hosts.Together,our findings uncover a default Th1 response to ample signal 1 and offer a means to selectively prime such protective responses by vaccination.